Rs, including FLT-3 ligand and stem cell aspect (32, 47). MICB and ULBP1 had been also shown to be upregulated on wholesome monocytes from glioblastoma patients in response to tumor-derived lactate dehydrogenase (48). Moreover, MICA and MICB have been observed on foam cells from atherosclerotic lesions as well as human monocyte-derived macrophages treated with acetylated low-density lipoprotein, mimicking atherosclerotic situations (49). A study by Ge et al. showed that though ULBP1 and MICA have been expressed at similar levels by PBMC from children with Kawasaki disease and healthy controls, NKG2D expression by NK cells and CD8+ T cells was decreased in diseased individuals, which correlated with elevated cytokine production by monocytes (50). This observation suggests that NKG2D ligand expressed by monocytes (and possiblyFrontiers in Immunology www.frontiersin.orgFebruary 2018 Volume 9 ArticleTrembath and MarkiewiczNKG2D Ligands on Immune Cellsearlier studies from our laboratory that demonstrate that higher NKG2D ligand expression decreases MHC class I expression by each tumor cells and standard cells (61). Although this reduce in MHC class I increases NK cell responses, it most likely decreases the response of CD8+ T cells (60, 61).OTHeR iMMUNe CeLLSMany studies report expression of mRNAs encoding NKG2D ligands in each main and secondary immune tissues (624). Considerably of this expression, especially in the thymus and spleen, is most likely attributed to immune cell forms currently discussed. Nevertheless, other immune cells have been found to express NKG2D ligands in both humans and mice, even though the function of this expression will not be totally clear. RAE-1 and H60 are expressed by freshly isolated bone marrow cells from Balb/c, but not C57BL/6 mice, and this expression is responsiblefor the rejection of Balb/c bone marrow by C57BL/6 mice in an NKG2D-dependent manner (65). GR-1+CD11b+F4/80+ myeloid-derived suppressor cells (MDSCs) from RMA-S tumor-bearing mice have been also identified to express RAE-1. This expression enhanced the production of IFN- by NK cells and made the MDSCs susceptible to NK cell killing each in vitro and in vivo (66). Similarly, tumor-infiltrating myeloid cells in glioblastoma patients were shown to express MICB and ULBP1 (48). It has yet to be determined if expression of NKG2D ligands in these instances is an incidental impact of fast cellular division in bone marrow or immune dysregulation in the tumor environment, or if they play a distinct function in immune cell development and regulation. However, offered the cellular power involved in protein expression, and also the potential immune triggering consequences, it appears unlikely that NKG2D ligands will be induced with out a biologically critical function.FiGURe 1 Visual summary of immunostimulatory and CLK Inhibitor Accession immunosuppressive effects of organic killer group 2 member D (NKG2D) ligand expression by cells with the immune BRD4 Inhibitor medchemexpress system. (A) The immunostimulatory effects of NKG2D ligand expression by immune cells. (1) NKG2D ligand expression by dendritic cells (DCs) and macrophages delivers activating and differentiation signals to NKG2D-bearing organic killer (NK) cells and CD8+ T cells. (2) Expression of NKG2D ligand by regulatory T cells (Tregs) targets these cells for killing by NK cells, thereby increasing the overall immune response. (3) NKG2D ligand expression could impact B cell cytokine production. (B) The immunosuppressive effects of NKG2D ligand expression by immune cells. (1) Widespread expression of NKG2D ligands.